Trial Outcomes & Findings for A Study to Evaluate Upadacitinib in Adolescents and Adults With Moderate to Severe Atopic Dermatitis (Measure Up 2) (NCT NCT03607422)

NCT ID: NCT03607422

Last Updated: 2025-12-03

Results Overview

EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/ neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 912 participants
• Primary outcome timeframe: Baseline and Week 16
• Results posted on: 2025-12-03

Participant Flow

Participants were enrolled at 154 study sites in 23 countries across Europe, North America, Oceania, and the Asia-Pacific region. The study included a 16-week double-blind treatment period followed by an ongoing blinded extension period. The first 836 adults and adolescents enrolled constituted the Main Study; additional adolescents were enrolled in the Adolescent Substudy to ensure enrollment of a total of 180 adolescent participants overall. Results are reported up to Week 16.

Participants were randomized equally into 1 of 3 treatment groups, stratified by disease severity (validated Investigator Global Assessment Scale for Atopic Dermatitis [vIGA-AD] moderate [3] vs severe [4]), geographic region (US/Puerto Rico/Canada vs Other), and age (adolescent [ages 12 to 17] vs adult [ages 18 to 75]). Randomization for the adolescent substudy was stratified by disease severity (vIGA-AD 3 vs vIGA-AD 4) and geographic region (US/Puerto Rico/Canada vs Other).

Participant milestones

Measure	Adults: Placebo Participants ≥ 18 years old received placebo orally once a day (QD) for 16 weeks.	Adults: Upadacitinib 15 mg QD Participants ≥ 18 years old received upadacitinib 15 mg orally once a day for 16 weeks.	Adults: Upadacitinib 30 mg QD Participants ≥ 18 years old received upadacitinib 30 mg orally once a day for 16 weeks.	Adolescents: Placebo Adolescent participants (12 - 17 years old) received placebo orally once a day for 16 weeks.	Adolescents: Upadacitinib 15 mg QD Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.	Adolescents: Upadacitinib 30 mg QD Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Study STARTED	242	243	247	60	58	62
Overall Study COMPLETED	204	233	235	55	55	59
Overall Study NOT COMPLETED	38	10	12	5	3	3

Reasons for withdrawal

Measure	Adults: Placebo Participants ≥ 18 years old received placebo orally once a day (QD) for 16 weeks.	Adults: Upadacitinib 15 mg QD Participants ≥ 18 years old received upadacitinib 15 mg orally once a day for 16 weeks.	Adults: Upadacitinib 30 mg QD Participants ≥ 18 years old received upadacitinib 30 mg orally once a day for 16 weeks.	Adolescents: Placebo Adolescent participants (12 - 17 years old) received placebo orally once a day for 16 weeks.	Adolescents: Upadacitinib 15 mg QD Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.	Adolescents: Upadacitinib 30 mg QD Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.
Overall Study Adverse Event	7	3	2	0	2	0
Overall Study Withdrawal by Subject	11	3	6	2	0	0
Overall Study Lost to Follow-up	0	0	1	0	0	0
Overall Study Other	12	4	1	2	0	2
Overall Study Ongoing at Time of Analysis	8	0	2	1	1	1

Baseline Characteristics

Participants with available data

Baseline characteristics by cohort

Measure	Adults: Placebo n=242 Participants Participants ≥ 18 years old received placebo orally once a day for 16 weeks.	Adults: Upadacitinib 15 mg QD n=243 Participants Participants ≥ 18 years old received upadacitinib 15 mg orally once a day for 16 weeks.	Adults: Upadacitinib 30 mg QD n=247 Participants Participants ≥ 18 years old received upadacitinib 30 mg orally once a day for 16 weeks.	Adolescents: Placebo n=60 Participants Adolescent participants received placebo orally once a day for 16 weeks.	Adolescents: Upadacitinib 15 mg QD n=58 Participants Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.	Adolescents: Upadacitinib 30 mg QD n=62 Participants Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.	Total n=912 Participants Total of all reporting groups
Age, Continuous	36.0 years STANDARD_DEVIATION 14.08 • n=242 Participants	35.7 years STANDARD_DEVIATION 15.15 • n=243 Participants	36.7 years STANDARD_DEVIATION 15.36 • n=247 Participants	15.5 years STANDARD_DEVIATION 1.67 • n=60 Participants	15.2 years STANDARD_DEVIATION 1.79 • n=58 Participants	15.8 years STANDARD_DEVIATION 1.70 • n=62 Participants	32.1 years STANDARD_DEVIATION 15.66 • n=912 Participants
Age, Customized 12 - 14 years	0 Participants n=242 Participants	0 Participants n=243 Participants	0 Participants n=247 Participants	18 Participants n=60 Participants	23 Participants n=58 Participants	15 Participants n=62 Participants	56 Participants n=912 Participants
Age, Customized 15 - 17 years	0 Participants n=242 Participants	0 Participants n=243 Participants	0 Participants n=247 Participants	42 Participants n=60 Participants	35 Participants n=58 Participants	47 Participants n=62 Participants	124 Participants n=912 Participants
Age, Customized 18 - < 40 years	161 Participants n=242 Participants	165 Participants n=243 Participants	161 Participants n=247 Participants	0 Participants n=60 Participants	0 Participants n=58 Participants	0 Participants n=62 Participants	487 Participants n=912 Participants
Age, Customized 40 - < 65 years	70 Participants n=242 Participants	63 Participants n=243 Participants	67 Participants n=247 Participants	0 Participants n=60 Participants	0 Participants n=58 Participants	0 Participants n=62 Participants	200 Participants n=912 Participants
Age, Customized ≥ 65 years	11 Participants n=242 Participants	15 Participants n=243 Participants	19 Participants n=247 Participants	0 Participants n=60 Participants	0 Participants n=58 Participants	0 Participants n=62 Participants	45 Participants n=912 Participants
Sex: Female, Male Female	104 Participants n=242 Participants	102 Participants n=243 Participants	103 Participants n=247 Participants	35 Participants n=60 Participants	38 Participants n=58 Participants	26 Participants n=62 Participants	408 Participants n=912 Participants
Sex: Female, Male Male	138 Participants n=242 Participants	141 Participants n=243 Participants	144 Participants n=247 Participants	25 Participants n=60 Participants	20 Participants n=58 Participants	36 Participants n=62 Participants	504 Participants n=912 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=242 Participants	18 Participants n=243 Participants	17 Participants n=247 Participants	10 Participants n=60 Participants	12 Participants n=58 Participants	11 Participants n=62 Participants	93 Participants n=912 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	217 Participants n=242 Participants	225 Participants n=243 Participants	230 Participants n=247 Participants	50 Participants n=60 Participants	46 Participants n=58 Participants	51 Participants n=62 Participants	819 Participants n=912 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=242 Participants	0 Participants n=243 Participants	0 Participants n=247 Participants	0 Participants n=60 Participants	0 Participants n=58 Participants	0 Participants n=62 Participants	0 Participants n=912 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=242 Participants	4 Participants n=243 Participants	1 Participants n=247 Participants	0 Participants n=60 Participants	2 Participants n=58 Participants	1 Participants n=62 Participants	13 Participants n=912 Participants
Race (NIH/OMB) Asian	52 Participants n=242 Participants	62 Participants n=243 Participants	55 Participants n=247 Participants	6 Participants n=60 Participants	5 Participants n=58 Participants	12 Participants n=62 Participants	192 Participants n=912 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=242 Participants	0 Participants n=243 Participants	0 Participants n=247 Participants	1 Participants n=60 Participants	2 Participants n=58 Participants	0 Participants n=62 Participants	4 Participants n=912 Participants
Race (NIH/OMB) Black or African American	15 Participants n=242 Participants	16 Participants n=243 Participants	17 Participants n=247 Participants	7 Participants n=60 Participants	5 Participants n=58 Participants	3 Participants n=62 Participants	63 Participants n=912 Participants
Race (NIH/OMB) White	165 Participants n=242 Participants	160 Participants n=243 Participants	172 Participants n=247 Participants	45 Participants n=60 Participants	42 Participants n=58 Participants	46 Participants n=62 Participants	630 Participants n=912 Participants
Race (NIH/OMB) More than one race	4 Participants n=242 Participants	1 Participants n=243 Participants	2 Participants n=247 Participants	1 Participants n=60 Participants	2 Participants n=58 Participants	0 Participants n=62 Participants	10 Participants n=912 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=242 Participants	0 Participants n=243 Participants	0 Participants n=247 Participants	0 Participants n=60 Participants	0 Participants n=58 Participants	0 Participants n=62 Participants	0 Participants n=912 Participants
Study Enrollment Main Study	242 Participants n=242 Participants	243 Participants n=243 Participants	247 Participants n=247 Participants	36 Participants n=60 Participants	33 Participants n=58 Participants	35 Participants n=62 Participants	836 Participants n=912 Participants
Study Enrollment Adolescent Substudy	0 Participants n=242 Participants	0 Participants n=243 Participants	0 Participants n=247 Participants	24 Participants n=60 Participants	25 Participants n=58 Participants	27 Participants n=62 Participants	76 Participants n=912 Participants
Geographic Region US/Puerto Rico/Canada	95 Participants n=242 Participants	95 Participants n=243 Participants	99 Participants n=247 Participants	25 Participants n=60 Participants	24 Participants n=58 Participants	27 Participants n=62 Participants	365 Participants n=912 Participants
Geographic Region Other	147 Participants n=242 Participants	148 Participants n=243 Participants	148 Participants n=247 Participants	35 Participants n=60 Participants	34 Participants n=58 Participants	35 Participants n=62 Participants	547 Participants n=912 Participants
vIGA-AD 3 (Moderate)	110 Participants n=242 Participants	111 Participants n=243 Participants	111 Participants n=247 Participants	26 Participants n=60 Participants	27 Participants n=58 Participants	29 Participants n=62 Participants	414 Participants n=912 Participants
vIGA-AD 4 (Severe)	132 Participants n=242 Participants	132 Participants n=243 Participants	136 Participants n=247 Participants	34 Participants n=60 Participants	31 Participants n=58 Participants	33 Participants n=62 Participants	498 Participants n=912 Participants
Eczema Area and Severity Index (EASI) Score	28.74 score on a scale STANDARD_DEVIATION 11.865 • n=241 Participants • Participants with available data	28.65 score on a scale STANDARD_DEVIATION 11.633 • n=243 Participants • Participants with available data	29.61 score on a scale STANDARD_DEVIATION 12.030 • n=247 Participants • Participants with available data	30.12 score on a scale STANDARD_DEVIATION 13.263 • n=60 Participants • Participants with available data	28.01 score on a scale STANDARD_DEVIATION 12.216 • n=58 Participants • Participants with available data	31.15 score on a scale STANDARD_DEVIATION 13.998 • n=62 Participants • Participants with available data	29.16 score on a scale STANDARD_DEVIATION 12.112 • n=911 Participants • Participants with available data
Disease Duration since Diagnosis	22.263 years STANDARD_DEVIATION 14.0798 • n=242 Participants • Participants with available data	19.802 years STANDARD_DEVIATION 13.8089 • n=243 Participants • Participants with available data	21.911 years STANDARD_DEVIATION 14.8401 • n=246 Participants • Participants with available data	12.169 years STANDARD_DEVIATION 4.7104 • n=60 Participants • Participants with available data	11.184 years STANDARD_DEVIATION 4.5479 • n=58 Participants • Participants with available data	12.128 years STANDARD_DEVIATION 4.6414 • n=62 Participants • Participants with available data	19.452 years STANDARD_DEVIATION 13.4892 • n=911 Participants • Participants with available data

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: The intent-to-treat population for the main study (ITT\_M) includes all participants who were randomized in the main study (adults and adolescents). Non-responder imputation incorporating multiple imputation to handle missing data due to coronavirus disease 2019 pandemic (COVID-19) (NRI-C) was used. The pre-specified primary analysis included participants enrolled in the main study only; Efficacy analyses of adolescent participants were conducted separately and are reported below.

EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/ neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).

The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.

Outcome measures

Measure	Upadacitinib 15 mg QD n=276 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=282 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=278 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving at Least a 75% Reduction in Eczema Area and Severity Index Score (EASI 75) From Baseline at Week 16	60.1 percentage of participants Interval 54.4 to 65.9	72.9 percentage of participants Interval 67.7 to 78.2	13.3 percentage of participants Interval 9.3 to 17.3

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for the main study; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale:

• 0 - Clear: No inflammatory signs of AD;
• 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification, no oozing or crusting;
• 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification, no oozing or crusting;
• 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, oozing or crusting may be present;
• 4 - Severe: Marked erythema, induration/papulation and/or lichenification; Oozing or crusting may be present.

Outcome measures

Measure	Upadacitinib 15 mg QD n=276 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=282 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=278 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 With a Reduction From Baseline of ≥ 2 Points at Week 16	38.8 percentage of participants Interval 33.0 to 44.5	52.0 percentage of participants Interval 46.1 to 57.9	4.7 percentage of participants Interval 2.2 to 7.2

SECONDARY outcome

Timeframe: Baseline (last available rolling average before the first dose of study drug) and Week 16

Population: Intent-to-treat population for the main study with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores.

Outcome measures

Measure	Upadacitinib 15 mg QD n=270 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=280 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=274 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus Numerical Rating Scale (NRS) at Week 16	41.9 percentage of participants Interval 36.0 to 47.7	59.6 percentage of participants Interval 53.9 to 65.4	9.1 percentage of participants Interval 5.7 to 12.5

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for the main study; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).

The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.

Outcome measures

Measure	Upadacitinib 15 mg QD n=276 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=282 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=278 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a 90% Reduction From Baseline in EASI Score (EASI 90) at Week 16	42.4 percentage of participants Interval 36.6 to 48.2	58.5 percentage of participants Interval 52.7 to 64.2	5.4 percentage of participants Interval 2.7 to 8.1

SECONDARY outcome

Timeframe: Baseline (last available rolling average before the first dose of study drug) and Week 4

Population: Intent-to-treat population for the main study with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores.

Outcome measures

Measure	Upadacitinib 15 mg QD n=270 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=280 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=274 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 4	48.9 percentage of participants Interval 42.9 to 54.9	60.7 percentage of participants Interval 55.0 to 66.4	3.6 percentage of participants Interval 1.4 to 5.9

SECONDARY outcome

Timeframe: Baseline and Week 2

Population: Intent-to-treat population for the main study; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).

The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.

An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.

Outcome measures

Measure	Upadacitinib 15 mg QD n=276 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=282 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=278 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving an EASI 75 Response at Week 2	33.0 percentage of participants Interval 27.4 to 38.5	44.0 percentage of participants Interval 38.2 to 49.8	3.6 percentage of participants Interval 1.4 to 5.8

SECONDARY outcome

Timeframe: Baseline (last available rolling average before the first dose of study drug) and Week 1

Population: Intent-to-treat population for the main study with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores.

Outcome measures

Measure	Upadacitinib 15 mg QD n=270 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=280 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=274 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 1	7.4 percentage of participants Interval 4.3 to 10.5	15.7 percentage of participants Interval 11.5 to 20.0	0.7 percentage of participants Interval 0.0 to 1.7

SECONDARY outcome

Timeframe: Baseline and Day 2

Population: Intent-to-treat population for the main study with Worst Pruritus NRS (daily score) ≥ 4 at Baseline; Non-responder imputation with no special data handling for missing data due to COVID-19 (NRI-NC) was used.

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11- point scale from 0 (no itch) to 10 (worst imaginable itch). The percentage of participants who had a 4-point or greater improvement from Baseline in Worst Pruritus NRS score at Day 2 was pre-specified as a ranked secondary endpoint for participants in the upadacitinib 30 mg group versus placebo group only.

Outcome measures

Measure	Upadacitinib 15 mg QD n=269 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=278 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=267 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 2	7.4 percentage of participants Interval 4.3 to 10.6	7.9 percentage of participants Interval 4.7 to 11.1	0.7 percentage of participants Interval 0.0 to 1.8

SECONDARY outcome

Timeframe: Baseline and Day 3

Population: Intent-to-treat population for the main study with Worst Pruritus NRS (daily score) ≥ 4 at Baseline; Non-responder imputation with no special data handling for missing data due to COVID-19 (NRI-NC) was used.

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).

The percentage of participants who had a 4-point or greater improvement in Worst Pruritus NRS score from Baseline at Day 3 was pre-specified as a ranked secondary endpoint for participants in the upadacitinib 15 mg group versus placebo group only.

Outcome measures

Measure	Upadacitinib 15 mg QD n=269 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=278 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=267 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 3	11.5 percentage of participants Interval 7.7 to 15.3	17.3 percentage of participants Interval 12.8 to 21.7	3.0 percentage of participants Interval 1.0 to 5.0

SECONDARY outcome

Timeframe: From first dose of study drug to Week 16

Population: Intent-to-treat population for the main study with an EASI score ≤ 65.4 at Baseline and at least one EASI post-baseline assessment prior to use of rescue medication.

A flare, characterized as a clinically meaningful worsening in EASI, is defined as an increase in EASI score of ≥ 6.6 points from Baseline during the double-blind treatment period and prior to use of any rescue medication. Flare was assessed in participants with an EASI score of 65.4 or less at Baseline.

Outcome measures

Measure	Upadacitinib 15 mg QD n=274 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=277 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=269 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Experiencing a Flare During the Double-blind Treatment Period	2.2 percentage of participants Interval 0.5 to 3.9	1.4 percentage of participants Interval 0.0 to 2.8	24.5 percentage of participants Interval 19.4 to 29.7

SECONDARY outcome

Timeframe: Baseline (last available rolling average before the first dose of study drug) and Week 16

Population: Intent-to-treat population for the main study with ADerm-IS Sleep Domain score ≥ 12 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The ADerm-IS is a 10-item patient reported outcome (PRO) questionnaire designed to assess a variety of impacts that participants experience from their AD.

The ADerm-IS sleep domain consists of 3 questions designed to assess the impact of AD on sleep on a daily basis over a 24-hour recall period. The items include difficulty falling asleep, impact on sleep, and waking at night. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The ADerm-IS sleep domain score is the sum of the 3 item scores and ranges from 0 (no impact) to 30 (worst impact). The ADerm-IS sleep domain was analyzed based on weekly rolling averages of daily scores.

The minimal clinically important difference for ADerm-IS sleep domain score is 12.

Outcome measures

Measure	Upadacitinib 15 mg QD n=219 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=228 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=233 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Reduction of ≥ 12 Points From Baseline in Atopic Dermatitis Impact Scale (ADerm-IS) Sleep Domain Score at Week 16	50.2 percentage of participants Interval 43.6 to 56.9	62.3 percentage of participants Interval 56.0 to 68.6	12.4 percentage of participants Interval 8.2 to 16.7

SECONDARY outcome

Timeframe: Baseline (last available rolling average before the first dose of study drug) and Week 16

Population: Intent-to-treat population for the main study with ADerm-SS Skin Pain Score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The ADerm-SS is an 11-item PRO questionnaire designed to assess signs and symptoms that patients may experience due to AD using a 24-hour recall period. For the skin pain item participants were asked on a daily basis to indicate how bad their worst skin pain due to AD was in the past 24 hours on an NRS from 0 (no pain) to 10 (worst imaginable pain). The ADerm-SS skin pain score was analyzed using weekly rolling averages of daily scores. The minimal clinically important difference for ADerm-SS skin pain score is 4.

Outcome measures

Measure	Upadacitinib 15 mg QD n=237 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=238 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=247 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain Score at Week 16	49.4 percentage of participants Interval 43.0 to 55.7	65.1 percentage of participants Interval 59.1 to 71.2	13.4 percentage of participants Interval 9.1 to 17.6

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for the main study with ADerm-SS TSS-7 ≥ 28 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The ADerm-SS is an 11-item questionnaire designed to assess signs and symptoms that participants may experience due to AD using a 24-hour recall period. The 7-item total symptom score includes 7 symptoms (items 1-7 of the ADerm-SS), each assessed on a NRS from 0 (no symptom) to 10 (worst imaginable). The 7 symptoms included in the score are itch while asleep, itch while awake, skin pain (each assessed daily), skin cracking, skin cracking pain, dry skin, and skin flaking (assessed weekly). The TSS-7 score ranges from 0 to 70, with higher scores indicating worsening symptoms. The minimal clinically important difference for ADerm-SS TSS-7 is 28.

Outcome measures

Measure	Upadacitinib 15 mg QD n=230 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=234 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=244 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Reduction of ≥ 28 Points From Baseline in ADerm-SS 7-Item Total Symptom Score (TSS-7) at Week 16	53.0 percentage of participants Interval 46.6 to 59.5	66.2 percentage of participants Interval 60.2 to 72.3	12.7 percentage of participants Interval 8.5 to 16.9

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for the main study with ADerm-IS Emotional State domain score ≥ 11 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD.

ADerm-IS emotional state sums three items [Items 8-10] measuring self-consciousness, embarrassment, and sadness with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The emotional state domain score ranges from 0 to 30, where higher scores represent worst impact.

The minimal clinically important difference for ADerm-IS emotional state domain score is 11.

Outcome measures

Measure	Upadacitinib 15 mg QD n=228 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=228 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=234 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Reduction of ≥ 11 Points From Baseline in ADerm-IS Emotional State Domain Score at Week 16	57.0 percentage of participants Interval 50.6 to 63.4	71.5 percentage of participants Interval 65.6 to 77.4	16.7 percentage of participants Interval 11.9 to 21.4

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for the main study with ADerm-IS Daily Activities Domain Score ≥ 14 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD.

ADerm-IS Daily Activities sums four items measuring limitations of household, physical, and social activities, and difficulty concentrating with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The daily activities domain score ranges from 0 to 40, where higher scores represent worst impact.

The minimal clinically important difference for the ADerm-IS daily activities domain score is 14.

Outcome measures

Measure	Upadacitinib 15 mg QD n=207 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=223 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=227 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Reduction of ≥ 14 Points From Baseline in ADerm-IS Daily Activities Domain Score at Week 16	57.0 percentage of participants Interval 50.3 to 63.7	69.5 percentage of participants Interval 63.5 to 75.5	18.9 percentage of participants Interval 13.8 to 24.0

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for the main study; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).

The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.

Outcome measures

Measure	Upadacitinib 15 mg QD n=276 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=282 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=278 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a 100% Reduction From Baseline in EASI Score (EASI 100) at Week 16	14.1 percentage of participants Interval 10.0 to 18.2	18.8 percentage of participants Interval 14.2 to 23.4	0.7 percentage of participants Interval 0.0 to 1.7

SECONDARY outcome

Timeframe: Baseline (last available rolling average before the first dose of study drug) and Week 16

Population: Intent-to-treat population for the main study with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements (MMRM) including observed measurements at all visits, except that measurements after any rescue medication were excluded.

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores. A negative change from Baseline indicates improvement.

Outcome measures

Measure	Upadacitinib 15 mg QD n=224 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=235 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=119 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percent Change From Baseline in Worst Pruritus NRS at Week 16	-51.20 percent change Interval -55.8 to -46.61	-66.49 percent change Interval -71.03 to -61.96	-17.04 percent change Interval -22.39 to -11.69

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for the main study with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements (MMRM) including observed measurements at all visits, except that measurements after any rescue medication were excluded.

EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1)] moderate [2], or severe [3]) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling - acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules - chronic eczema).

The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from Baseline indicates improvement.

Outcome measures

Measure	Upadacitinib 15 mg QD n=246 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=250 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=142 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percent Change From Baseline in EASI Score at Week 16	-74.13 percent change Interval -78.45 to -69.82	-84.65 percent change Interval -88.93 to -80.37	-34.51 percent change Interval -39.6 to -29.42

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for the main study with POEM score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The POEM is a 7-item, validated questionnaire used to assess disease symptoms in both children and adults.

Participants respond to 7 questions, including dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping, each scored on a 5-point scale based on frequency of occurrence during the previous week: 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days. Item scores are added to provide a total score ranging from 0 (clear) to 28 (very severe atopic eczema). A change in POEM score of 3.4 points is considered the minimal clinically important difference.

Outcome measures

Measure	Upadacitinib 15 mg QD n=268 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=269 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=268 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Patient Oriented Eczema Measure (POEM) Total Score at Week 16	70.9 percentage of participants Interval 65.5 to 76.3	83.5 percentage of participants Interval 79.1 to 88.0	28.7 percentage of participants Interval 23.3 to 34.1

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for the main study who were ≥ 16 years old at Screening with DLQI score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much).

Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL.

the DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit.

Outcome measures

Measure	Upadacitinib 15 mg QD n=251 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=251 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=250 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Dermatology Life Quality Index (DLQI) at Week 16	71.7 percentage of participants Interval 66.1 to 77.3	77.6 percentage of participants Interval 72.5 to 82.8	28.4 percentage of participants Interval 22.8 to 34.0

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for the main study with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements (MMRM) including observed measurements at all visits, except that measurements after any rescue medication were excluded.

SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A negative change from Baseline indicates improvement.

Outcome measures

Measure	Upadacitinib 15 mg QD n=245 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=241 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=136 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16	-57.90 percent change Interval -61.84 to -53.97	-68.44 percent change Interval -72.44 to -64.44	-28.43 percent change Interval -33.34 to -23.52

SECONDARY outcome

Timeframe: Week 16

Population: Intent-to-treat population for the main study with HADS-A ≥ 8 or HADS-D ≥ 8 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The HADS is a 14-item questionnaire, with seven items related to anxiety (HADS-A) and seven items related to depression (HADS-D). Each item is scored from 0 to 3; scores for each subscale range from 0 to 21, with higher scores indicating more distress. For each domain, scores 7 or lower are considered normal, 8 to 10 are borderline, and 11 or higher indicate clinical anxiety or depression.

Outcome measures

Measure	Upadacitinib 15 mg QD n=137 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=146 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=140 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a Hospital Anxiety and Depression Scale-Anxiety (HADS-A) Score and Hospital Anxiety and Depression Scale-Depression (HADS-D) Score of < 8 at Week 16	46.0 percentage of participants Interval 37.6 to 54.3	56.1 percentage of participants Interval 48.1 to 64.2	11.4 percentage of participants Interval 6.2 to 16.7

SECONDARY outcome

Timeframe: Week 16

Population: Intent-to-treat population for the main study who were ≥ 16 years old at Screening with DLQI score \> 1 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much).

Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. A score of 0 or 1 means that the disease has no effect at all.

The DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit.

Outcome measures

Measure	Upadacitinib 15 mg QD n=252 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=256 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=257 Participants Participants received placebo orally once a day for 16 weeks.
Main Study: Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 16	23.8 percentage of participants Interval 18.6 to 29.1	37.9 percentage of participants Interval 32.0 to 43.9	4.7 percentage of participants Interval 2.1 to 7.2

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: The ITT population for adolescents (ITT\_A) consists of all adolescent participants who were randomized in the main study or the adolescent sub-study. Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).

The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.

An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.

Outcome measures

Measure	Upadacitinib 15 mg QD n=58 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=62 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=60 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 16	69.0 percentage of participants Interval 57.1 to 80.9	73.4 percentage of participants Interval 62.3 to 84.6	13.3 percentage of participants Interval 4.7 to 21.9

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: The ITT population for adolescents; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale:

• 0 - Clear: No signs of AD;
• 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification, no oozing or crusting;;
• 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification, no oozing or crusting;
• 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, possible oozing or crusting;
• 4 - Severe: Marked erythema, induration/papulation and/or lichenification; possible oozing or crusting.

Outcome measures

Measure	Upadacitinib 15 mg QD n=58 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=62 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=60 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a vIGA-AD of 0 or 1 With a Reduction From Baseline of ≥ 2 Points at Week 16	44.8 percentage of participants Interval 32.0 to 57.6	59.4 percentage of participants Interval 47.0 to 71.8	5.0 percentage of participants Interval 0.0 to 10.5

SECONDARY outcome

Timeframe: Baseline (last available rolling average before the first dose of study drug) and Week 16

Population: Intent-to-treat population for adolescents with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores.

Outcome measures

Measure	Upadacitinib 15 mg QD n=55 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=60 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=59 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 16	38.2 percentage of participants Interval 25.3 to 51.0	56.7 percentage of participants Interval 44.1 to 69.2	3.4 percentage of participants Interval 0.0 to 8.0

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for adolescents; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).

The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.

An EASI 90 response is defined as at least a 90% reduction (improvement) from Baseline in EASI score.

Outcome measures

Measure	Upadacitinib 15 mg QD n=58 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=62 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=60 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving an EASI 90 Response at Week 16	48.3 percentage of participants Interval 35.4 to 61.1	62.0 percentage of participants Interval 49.8 to 74.3	1.7 percentage of participants Interval 0.0 to 4.9

SECONDARY outcome

Timeframe: Baseline (last available rolling average before the first dose of study drug) and Week 4

Population: Intent-to-treat population for adolescents with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores.

Outcome measures

Measure	Upadacitinib 15 mg QD n=55 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=60 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=59 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 4	38.2 percentage of participants Interval 25.3 to 51.0	50.0 percentage of participants Interval 37.3 to 62.7	3.4 percentage of participants Interval 0.0 to 8.0

SECONDARY outcome

Timeframe: Baseline and Week 2

Population: The ITT population for adolescents; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).

The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.

An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.

Outcome measures

Measure	Upadacitinib 15 mg QD n=58 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=62 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=60 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 2	37.9 percentage of participants Interval 25.4 to 50.4	53.2 percentage of participants Interval 40.8 to 65.6	6.7 percentage of participants Interval 0.4 to 13.0

SECONDARY outcome

Timeframe: Baseline (last available rolling average before the first dose of study drug) and Week 1

Population: Intent-to-treat population for adolescents with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores.

Outcome measures

Measure	Upadacitinib 15 mg QD n=55 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=60 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=59 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 1	12.7 percentage of participants Interval 3.9 to 21.5	5.0 percentage of participants Interval 0.0 to 10.5	0.0 percentage of participants Could not be calculated using the normal approximation to the binomial distribution

SECONDARY outcome

Timeframe: Baseline and Day 2

Population: Intent-to-treat population for adolescents with Worst Pruritus NRS (daily score) ≥ 4 at Baseline; Non-responder imputation with no special data handling for missing data due to COVID-19 was used.

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).

Outcome measures

Measure	Upadacitinib 15 mg QD n=56 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=62 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=59 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 2	8.9 percentage of participants Interval 1.5 to 16.4	3.2 percentage of participants Interval 0.0 to 7.6	0.0 percentage of participants Could not be calculated using the normal approximation to the binomial distribution

SECONDARY outcome

Timeframe: Baseline and Day 3

Population: Intent-to-treat population for adolescents with Worst Pruritus NRS (daily score) ≥ 4 at Baseline; Non-responder imputation with no special data handling for missing data due to COVID-19 was used.

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).

Outcome measures

Measure	Upadacitinib 15 mg QD n=56 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=62 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=59 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 3	14.3 percentage of participants Interval 5.1 to 23.5	9.7 percentage of participants Interval 2.3 to 17.0	1.7 percentage of participants Interval 0.0 to 5.0

SECONDARY outcome

Timeframe: From first dose of study drug to Week 16

Population: Intent-to-treat population for adolescents with an EASI score ≤ 65.4 at Baseline and at least one EASI post-baseline assessment prior to use of rescue medication.

A flare, characterized as a clinically meaningful worsening in EASI, is defined as an increase in EASI score of ≥ 6.6 points from Baseline during the double-blind treatment period and prior to use of any rescue medication. Flares were assessed in participants with an EASI score of 65.4 or less at Baseline.

Outcome measures

Measure	Upadacitinib 15 mg QD n=58 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=61 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=60 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Experiencing a Flare During the Double-blind Treatment Period	1.7 percentage of participants Interval 0.0 to 5.1	1.6 percentage of participants Interval 0.0 to 4.8	20.0 percentage of participants Interval 9.9 to 30.1

SECONDARY outcome

Timeframe: Baseline (last available rolling average before the first dose of study drug) and Week 16

Population: Intent-to-treat population for adolescents with ADerm-IS Sleep Domain score ≥ 12 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The ADerm-IS is a 10-item patient reported outcome questionnaire designed to assess a variety of impacts that participants experience from their AD.

The ADerm-IS sleep domain consists of 3 questions designed to assess the impact of AD on sleep on a daily basis over a 24-hour recall period. The items include difficulty falling asleep, impact on sleep, and waking at night. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The ADerm-IS sleep domain score is the sum of the 3 item scores and ranges from 0 (no impact) to 30 (worst impact). The ADerm-IS sleep domain was analyzed based on weekly rolling averages of daily scores.

The minimal clinically important difference for ADerm-IS sleep domain score is 12.

Outcome measures

Measure	Upadacitinib 15 mg QD n=40 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=44 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=42 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a Reduction of ≥ 12 Points From Baseline in ADerm-IS Sleep Domain Score at Week 16	37.5 percentage of participants Interval 22.5 to 52.5	61.4 percentage of participants Interval 47.0 to 75.8	9.5 percentage of participants Interval 0.6 to 18.4

SECONDARY outcome

Timeframe: Baseline (last available rolling average before the first dose of study drug) and Week 16

Population: Intent-to-treat population for adolescents with ADerm-SS Skin Pain score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The ADerm-SS is an 11-item PRO questionnaire designed to assess signs and symptoms that patients may experience due to AD using a 24-hour recall period. For the skin pain item participants were asked to indicate on a daily basis how bad their worst skin pain due to AD was in the past 24 hours on an NRS from 0 (no pain) to 10 (worst imaginable pain).

The minimal clinically important difference for ADerm-SS skin pain score is 4. The ADerm-SS skin pain score was analyzed based on weekly rolling averages of daily scores.

Outcome measures

Measure	Upadacitinib 15 mg QD n=48 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=51 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=53 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in ADerm-SS Skin Pain Score at Week 16	39.6 percentage of participants Interval 25.7 to 53.4	60.8 percentage of participants Interval 47.4 to 74.2	7.5 percentage of participants Interval 0.4 to 14.7

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for adolescents with ADerm-SS TSS-7 ≥ 28 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The ADerm-SS is an 11-item questionnaire designed to assess signs and symptoms that participants may experience due to AD using a 24-hour recall period. The 7-item total symptom score includes 7 symptoms (items 1-7 of the ADerm-SS), each assessed on a NRS from 0 (no symptom) to 10 (worst imaginable). The 7 symptoms included in the score are itch while asleep, itch while awake, skin pain (each assessed daily), skin cracking, skin cracking pain, dry skin, and skin flaking (assessed weekly). The TSS-7 score ranges from 0 to 70, with higher scores indicating worsening symptoms. The minimal clinically important difference for ADerm-SS TSS-7 is 28.

Outcome measures

Measure	Upadacitinib 15 mg QD n=48 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=55 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=55 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a Reduction of ≥ 28 Points From Baseline in ADerm-SS TSS-7 at Week 16	47.9 percentage of participants Interval 33.8 to 62.0	60.0 percentage of participants Interval 47.1 to 72.9	10.9 percentage of participants Interval 2.7 to 19.1

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for adolescents with ADerm-IS Emotional State Domain score ≥ 11 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD.

ADerm-IS emotional state sums three items [Items 8-10] measuring self-consciousness, embarrassment, and sadness with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The emotional state domain score ranges from 0 to 30, where higher scores represent worst impact.

The minimal clinically important difference for ADerm-IS emotional state domain score is 11.

Outcome measures

Measure	Upadacitinib 15 mg QD n=45 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=50 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=50 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a Reduction of ≥ 11 Points From Baseline in ADerm-IS Emotional State Domain Score at Week 16	60.0 percentage of participants Interval 45.7 to 74.3	72.0 percentage of participants Interval 59.6 to 84.4	18.0 percentage of participants Interval 7.4 to 28.6

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for adolescents with ADerm-IS Daily Activities Domain Score ≥ 14 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD.

ADerm-IS daily activities sums four items measuring limitations of household, physical, and social activities, and difficulty concentrating with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The daily activities domain score ranges from 0 to 40, where higher scores represent worst impact.

The minimal clinically important difference for the ADerm-IS daily activities domain score is 14.

Outcome measures

Measure	Upadacitinib 15 mg QD n=40 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=50 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=49 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a Reduction of ≥ 14 Points From Baseline in ADerm-IS Daily Activities Domain Score at Week 16	52.5 percentage of participants Interval 37.0 to 68.0	68.0 percentage of participants Interval 55.1 to 80.9	22.4 percentage of participants Interval 10.8 to 34.1

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: The ITT population for adolescents; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).

The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.

An EASI 100 response is defined as a 100% reduction (improvement) from Baseline in EASI score.

Outcome measures

Measure	Upadacitinib 15 mg QD n=58 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=62 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=60 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving an EASI 100 Response at Week 16	15.5 percentage of participants Interval 6.2 to 24.8	19.4 percentage of participants Interval 9.5 to 29.2	1.7 percentage of participants Interval 0.0 to 4.9

SECONDARY outcome

Timeframe: Baseline (last available rolling average before the first dose of study drug) and Week 16

Population: Intent-to-treat population for adolescents with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements including observed measurements at all visits, except that measurements after any rescue medication were excluded.

Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores. A negative change from Baseline indicates improvement.

Outcome measures

Measure	Upadacitinib 15 mg QD n=49 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=55 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=27 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percent Change From Baseline in Worst Pruritus NRS at Week 16	-47.56 percent change Interval -57.0 to -38.13	-66.95 percent change Interval -76.07 to -57.84	-11.02 percent change Interval -22.14 to 0.1

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for adolescents with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements including observed measurements at all visits, except that measurements after any rescue medication were excluded.

EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1)] moderate [2], or severe [3]) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling - acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules - chronic eczema).

The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from Baseline indicates improvement.

Outcome measures

Measure	Upadacitinib 15 mg QD n=53 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=52 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=31 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percent Change From Baseline in EASI Score at Week 16	-77.85 percent change Interval -85.95 to -69.74	-84.81 percent change Interval -92.84 to -76.78	-42.19 percent change Interval -52.06 to -32.33

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for adolescents with POEM score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The POEM is a 7-item, validated questionnaire used to assess disease symptoms in both children and adults. Participants respond to 7 questions, including dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping, each scored on a 5-point scale based on frequency of occurrence during the previous week: 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days. Item scores are added to provide a total score ranging from 0 (clear) to 28 (very severe atopic eczema). A change in POEM score of 3.4 points is considered the minimal clinically important difference.

Outcome measures

Measure	Upadacitinib 15 mg QD n=56 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=57 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=57 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in POEM Total Score at Week 16	66.1 percentage of participants Interval 53.7 to 78.5	80.7 percentage of participants Interval 70.5 to 90.9	28.1 percentage of participants Interval 16.4 to 39.7

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for adolescents who were ≥ 16 years old at Screening with DLQI score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much).

Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL.

the DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit.

Outcome measures

Measure	Upadacitinib 15 mg QD n=22 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=30 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=26 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in DLQI Score at Week 16	68.2 percentage of participants Interval 48.7 to 87.6	73.3 percentage of participants Interval 57.5 to 89.2	19.2 percentage of participants Interval 4.1 to 34.4

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-treat population for adolescents with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements including observed measurements at all visits, except that measurements after any rescue medication were excluded.

SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A negative change from Baseline indicates improvement.

Outcome measures

Measure	Upadacitinib 15 mg QD n=54 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=49 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=30 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percent Change From Baseline in SCORAD Score at Week 16	-57.89 percent change Interval -65.49 to -50.28	-72.81 percent change Interval -80.77 to -64.85	-27.91 percent change Interval -37.98 to -17.83

SECONDARY outcome

Timeframe: Week 16

Population: Intent-to-treat population for adolescents with HADS-A ≥ 8 or HADS-D ≥ 8 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The HADS is a 14-item questionnaire, with seven items related to anxiety (HADS-A) and seven items related to depression (HADS-D). Each item is scored from 0 to 3; scores for each subscale range from 0 to 21, with higher scores indicating more distress. For each domain, scores 7 or lower are considered normal, 8 to 10 are borderline, and 11 or higher indicate clinical anxiety or depression.

Outcome measures

Measure	Upadacitinib 15 mg QD n=24 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=32 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=25 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving HADS-A Score and HADS-D Score of < 8 at Week 16	37.5 percentage of participants Interval 18.1 to 56.9	43.8 percentage of participants Interval 26.6 to 60.9	16.0 percentage of participants Interval 1.6 to 30.4

SECONDARY outcome

Timeframe: Week 16

Population: Intent-to-treat population for adolescents who were ≥ 16 years old at Screening with DLQI score \> 1 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used.

The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much).

Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. A score of 0 or 1 means that the disease has no effect at all.

the DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit.

Outcome measures

Measure	Upadacitinib 15 mg QD n=22 Participants Participants received upadacitinib 15 mg orally once a day for 16 weeks.	Upadacitinib 30 mg QD n=32 Participants Participants received upadacitinib 30 mg orally once a day for 16 weeks.	Placebo n=26 Participants Participants received placebo orally once a day for 16 weeks.
Adolescents: Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 16	13.6 percentage of participants Interval 0.0 to 28.0	46.9 percentage of participants Interval 29.6 to 64.2	7.7 percentage of participants Interval 0.0 to 17.9

Adverse Events

Adults: Upadacitinib 30 mg QD

Serious events: 7 serious events

Other events: 94 other events

Deaths: 0 deaths

Adolescents: Placebo

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Adolescents: Upadacitinib 15 mg QD

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Adolescents: Upadacitinib 30 mg QD

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Adults: Placebo

Serious events: 6 serious events

Other events: 52 other events

Deaths: 0 deaths

Adults: Upadacitinib 15 mg QD

Serious events: 3 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Measure	Adults: Upadacitinib 30 mg QD n=247 participants at risk Participants ≥ 18 years old received upadacitinib 30 mg orally once a day for 16 weeks.	Adolescents: Placebo n=60 participants at risk Adolescent participants received placebo orally once a day for 16 weeks.	Adolescents: Upadacitinib 15 mg QD n=58 participants at risk Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.	Adolescents: Upadacitinib 30 mg QD n=62 participants at risk Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.	Adults: Placebo n=242 participants at risk Participants ≥ 18 years old received placebo orally once a day for 16 weeks.	Adults: Upadacitinib 15 mg QD n=243 participants at risk Participants ≥ 18 years old received upadacitinib 15 mg orally once a day for 16 weeks.
Infections and infestations ORCHITIS	0.40% 1/247 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Eye disorders RETINAL DETACHMENT	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.41% 1/243 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Eye disorders RETINAL TEAR	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.41% 1/243 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
General disorders INFLUENZA LIKE ILLNESS	0.40% 1/247 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Infections and infestations CELLULITIS	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.7% 1/60 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Infections and infestations ECZEMA HERPETICUM	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.41% 1/243 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Infections and infestations IMPETIGO	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.41% 1/242 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Infections and infestations PNEUMONIA	0.40% 1/247 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Infections and infestations SUBCUTANEOUS ABSCESS	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.7% 1/60 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Injury, poisoning and procedural complications FALL	0.40% 1/247 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Injury, poisoning and procedural complications HEAT STROKE	0.40% 1/247 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.41% 1/242 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Musculoskeletal and connective tissue disorders RHABDOMYOLYSIS	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.41% 1/243 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ANAL SQUAMOUS CELL CARCINOMA	0.40% 1/247 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Nervous system disorders MIGRAINE	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.7% 1/60 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Psychiatric disorders BIPOLAR DISORDER	0.40% 1/247 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Psychiatric disorders SUICIDE ATTEMPT	0.40% 1/247 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.7% 1/58 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.41% 1/242 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Respiratory, thoracic and mediastinal disorders PNEUMOMEDIASTINUM	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.7% 1/58 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.41% 1/242 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Skin and subcutaneous tissue disorders DERMATITIS ATOPIC	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.7% 1/60 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.7% 1/58 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.83% 2/242 • Number of events 2 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Skin and subcutaneous tissue disorders ECZEMA	0.00% 0/247 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.41% 1/242 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Vascular disorders HYPERTENSIVE EMERGENCY	0.40% 1/247 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/58 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/243 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.

Other adverse events

Measure	Adults: Upadacitinib 30 mg QD n=247 participants at risk Participants ≥ 18 years old received upadacitinib 30 mg orally once a day for 16 weeks.	Adolescents: Placebo n=60 participants at risk Adolescent participants received placebo orally once a day for 16 weeks.	Adolescents: Upadacitinib 15 mg QD n=58 participants at risk Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks.	Adolescents: Upadacitinib 30 mg QD n=62 participants at risk Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks.	Adults: Placebo n=242 participants at risk Participants ≥ 18 years old received placebo orally once a day for 16 weeks.	Adults: Upadacitinib 15 mg QD n=243 participants at risk Participants ≥ 18 years old received upadacitinib 15 mg orally once a day for 16 weeks.
Respiratory, thoracic and mediastinal disorders ASTHMA	0.81% 2/247 • Number of events 2 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	5.2% 3/58 • Number of events 5 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	3.2% 2/62 • Number of events 3 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/242 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.41% 1/243 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	1.6% 4/247 • Number of events 5 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	6.9% 4/58 • Number of events 4 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	3.2% 2/62 • Number of events 2 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.7% 4/242 • Number of events 4 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.6% 4/243 • Number of events 4 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Skin and subcutaneous tissue disorders ACNE	15.4% 38/247 • Number of events 39 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	3.3% 2/60 • Number of events 2 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	10.3% 6/58 • Number of events 6 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	14.5% 9/62 • Number of events 10 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	2.1% 5/242 • Number of events 5 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	12.8% 31/243 • Number of events 32 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Skin and subcutaneous tissue disorders DERMATITIS ATOPIC	0.81% 2/247 • Number of events 2 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	13.3% 8/60 • Number of events 8 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.7% 1/58 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.6% 1/62 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	7.0% 17/242 • Number of events 19 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	2.9% 7/243 • Number of events 7 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	5.7% 14/247 • Number of events 19 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.7% 1/60 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	10.3% 6/58 • Number of events 6 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	4.8% 3/62 • Number of events 3 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	4.5% 11/242 • Number of events 13 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	5.3% 13/243 • Number of events 14 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Investigations BLOOD CREATINE PHOSPHOKINASE INCREASED	4.0% 10/247 • Number of events 10 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.7% 1/60 • Number of events 1 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	5.2% 3/58 • Number of events 3 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	9.7% 6/62 • Number of events 6 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	1.7% 4/242 • Number of events 5 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	3.3% 8/243 • Number of events 8 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Nervous system disorders HEADACHE	6.5% 16/247 • Number of events 17 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	3.3% 2/60 • Number of events 4 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	5.2% 3/58 • Number of events 4 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	8.1% 5/62 • Number of events 6 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	4.1% 10/242 • Number of events 11 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	7.0% 17/243 • Number of events 20 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
General disorders FATIGUE	3.2% 8/247 • Number of events 9 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/60 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	5.2% 3/58 • Number of events 3 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.83% 2/242 • Number of events 2 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.82% 2/243 • Number of events 2 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.
Infections and infestations NASOPHARYNGITIS	7.3% 18/247 • Number of events 18 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	3.3% 2/60 • Number of events 2 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	3.4% 2/58 • Number of events 2 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	0.00% 0/62 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	4.5% 11/242 • Number of events 20 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.	5.8% 14/243 • Number of events 17 • From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period.

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